The purpose of this application is to request a renewal of my Research Scientist Award (RSA). The Research Scientist Development Award (1972-1982) and the RSA Award (1983- present) have permitted me the flexibility to accept only those responsibilities, such as teaching and administration, which I determined appropriate for my overall career development. As a result, I believe I have been able to systematically expand and enhance my research program which otherwise would not have been possible. My research interest are in the effects of adolescent exposure to two widely abused drugs, morphine and alcohol, on the onset of puberty and sexual maturation in the male and the possibility that the abuse of these drugs could lead to effects on fertility and the sexual development of their progeny. To accomplish these goals we have several broad objectives: first, to examine whether exposure to morphine or alcohol during the pre- early, mid- and late pubertal phases influences the onset of puberty and sexual maturation as reflected in thos characteristic changes occurring in the hypothalamus, pituitary and gonads; second, to determine the dose- and time-response characteristics of these effects; and, finally, to examine whether the effects of early morphine or alcohol exposure are reversible or rather leave a lasting impirnt. The second facit of our research is whether paternal, pregestational exposure to morphine and alcohol influences the generation of viable offspring, subsequent to mating with drug-naive females, particularly with respect to their reproductive status. The aims of these studies will be: first, to determine the extent and nature of the deficits in the male offspring sired by fathers exposed to morphine and alcohol prior to mating; second, to examine whether the onset of puberty and sexual maturation are influenced; and, finally, to examine whether there are critical periods in the male during which exposure to these two drugs produce particularly adverse effects on their offspring. The significance of our research is two-fold. First, human adolescent drug abuse is becoming an increasing concern and we know very little about is long-term consequences. Second, although it is recognized that the use of drugs during pregnancy may adversely affect fetal outcome, we know very little about whether paternal drug abuse could also contribute to birth defects. Our studies should shed some light on these important issues.